We recently have demonstrated that in vivo phosphorus magnetic resonance spectroscopy (31P MRS) provide metabolic signatures that predict treatment outcomes to standard treatment in non Hodgkin's lymphomas (NHL).1-9 The goal of the present proposal is to extend these results and demonstrate the value of 31P and hydrogen (1H) MRS at 3.0 Tesla acquired non-invasively and during the same visit in providing metabolic signatures to predict clinical outcome in NHL patients undergoing non-standard (experimental) treatment. If successful, these methods can be used to individually tailor the new treatments available for lymphoma patients with a potential increase in therapeutic success rates. Thus, the central aim of this proposal is to determine if the metabolic profiles determined non-invasively by in vivo 31P and 1H MRS are an independent a priori predictor of tumor therapy outcome in NHL patients, whom are going to receive non-standard therapy. Our clinical colleagues agree that successful achievement of this aim would help guide the use of more aggressive and novel therapies after a lymphoma patient has shown to be unresponsive to standard therapies. With the initial demonstration of our hypothesis in this proposal, we plan its extension into a multi-center research proposal aiming to accrue a larger patient cohort to formally validate the initial results. We believe that the expenses of the present proposal and its extension into a multi-center study are justified by the potential utility and economic impact of the results;namely to be able to tailor-fit novel therapies to the metabolic profile of an individual patient. We plan to study tumor areas of 30 non Hodgkin's lymphoma patients using noninvasive 31P and 1H MRS technology at 3.0 Tesla before and during the course of receiving non-standard therapy. We will follow-up the patients clinically to correlate the MRS results with objective measures of their therapeutic outcome namely long-term response to treatment and disease-free survival. In addition, the same tumor area of ten of these patients will be studied using 31P MRS at 1.5 Tesla before receiving therapy so a comparison factor can be found between the two magnetic field strengths. In this way, the data obtained at 1.5 Tesla can be compared with the data obtained at 3.0 Tesla. PUBLIC HEALTH RELEVANCE: In a previous work, we studied the chemistry of the tumors of patients with non-Hodgkin's lymphoma (a form of cancer of the lymph nodes) with a method called magnetic resonance spectroscopy that is non-invasive (meaning that it does not need x-rays, biopsies or needles). In the previous work, the chemistry of the tumors that we studied allowed us to predict if the tumor was going to respond to the drugs commonly given to treat the disease before the patients were treated. In the present work, we want to extend our findings by studying non-Hodgkin's lymphoma patients that already received the commonly given anti-cancer drugs and their tumor either failed to respond to treatment (the tumor did not go away) or came back once again, and that are now scheduled to receive non-standard (experimental) drugs. If we are successful, the non-invasive study of the chemistry of the tumors will allow us to predict and to follow-up whether or not the tumor is responding to the non-standard (experimental) treatment as we have predicted the response to standard treatment. This research will impact public health by identifying in advance if the patients with lymphoma will or will not respond to the newer treatment allowing doctors to tailor-fit the treatment on these patients by avoiding ineffective treatments preventing side-effects, waste of money, and waste of valuable time.